Macrophages and Brucella.

The studies reviewed here indicate that during the course of infection with B. abortus protective immune responses occur and that macrophages are activated for antimicrobial activity in both susceptible and resistant animals. Yet in susceptible animals chronic infections with B. abortus become established. There is circumstantial evidence from experiments in vitro that the outcome of infection is related to macrophage/Brucella interactions. This includes the following: 1) the virulence of strains of B. abortus is proportional to their ability to inhibit host phagocyte functions and to survive in murine, bovine, and guinea pig macrophages; and 2) the ability of guinea pig and bovine macrophages to inhibit intracellular growth of brucellae is directly proportional to the innate resistance of the host from which the macrophages were derived. In the murine model, the relative resistance of C57Bl/10 mice to infection with virulent B. abortus strain 2308 correlated with more efficient clearance during the first week following infection, compared with the susceptible BALB/c strain. It is not known whether this was due to innate differences in the recruitment or bactericidal activities of macrophage populations in the two mouse strains, as demonstrated with L. monocytogenes, or to other nonimmune factors such as natural killer cells secreting IFN-gamma and lysing infected macrophages following direct interaction with the brucellae, as shown with other intracellular bacteria. It is also of interest that clearance of strain 2308 following the plateau phase was slower in BALB/c than in C57Bl/10 mice. Since at this time protective T cells are known to be present in the spleens of BALB/c mice, this difference may have been due either to more efficient clearance of brucellae by C57Bl/10 macrophages following activation with T cell cytokines, or to the inability of immune T cells to interact with Brucella-infected macrophages in the susceptible BALB/c strain. CD8 T cells have been shown to have an important role in clearance of brucellae following the peak of infection and may act by lysing chronically infected macrophages. Although protective T cells have been demonstrated in susceptible strains of mice, chronically infected macrophages in these animals may fail to act as targets or may down-regulate T cell functions. As a result, infected macrophages could persist in the presence of Brucella-specific T cells.(ABSTRACT TRUNCATED AT 400 WORDS)